一例Fechtner综合征临床与分子缺陷研究——附文献复习

Clinical and molecular study on Fechtner syndrome ——case report and literature review

目的对1例Fechtner综合征先证者及其家系进行临床与实验室研究并检测非肌性肌球蛋白重链9基因（MYH9）突变。方法采用瑞特染色观察先证者及其家系患者的外周血涂片血小板和中性粒细胞的特殊形态；透射电镜观察先证者血小板及中性粒细胞的超微结构。从先证者及其家系成员外周血白细胞中提取基因组DNA，PCR扩增MYH9的40个外显子及侧翼内含子序列，检测其基因突变。结果该家系中Fechtner综合征患者表现为血小板减少、巨大血小板、中性粒细胞包涵体，伴或不伴遗传性肾炎。先证者及其家系患病成员的MYH9改变为外显子40第5981位核苷酸C-T杂合改变，使第1933位密码子CGA（编码Arg）突变为终止密码TGA。结论国内首次报道Fechtner综合征家系。MYH9（外显子40）R1933X杂合改变是导致Fechtner综合征的原因。

Objective To identify clinical and laboratory abnormalities and genetic defect of Fechtnet syndrome in a Chinese family. Methods The characteristic morphological features of platelets and leukocytes were examined on blood smears with Wright＇ s-Giemsa staining and uhrastructure of platelet and leukocyte were investigated under electron microscope. Genomic DNA was isolated from peripheral blood of the proband and 9 members of his family. All the exons and exon-intron boundaries of the MYH9 gene were amplified by PCR followed by direct sequencing. Results Patients presented the characteristic clinical features including macrothrombocytopenia,leukocyte inclusions and/or hereditary nephritis. A heterozygous C to T mutation was found in the proband and three members of his family at nucleotide 5981 in exon 40 of MYH9 gene, resulting in a nonsense mutation which encoded truncated protein due to premature termination at the Arg 1933 eodon. Conclusion It is the first report of a Chinese family with Fechtner syndrome. The Arg（CGA） 1933→stop（TGA） nonsense mutation in MYH9 gene is a causative genetic defect.